Development of artificial transcription factors for the treatment of lung and esophageal squamous cell carcinoma
| Project/Area Number |
26462141
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Respiratory surgery
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
世良 貴史 岡山大学, 自然科学研究科, 教授 (10362443)
深澤 拓也 川崎医科大学, 医学部, 准教授 (20379845)
山辻 知樹 川崎医科大学, 医学部, 准教授 (40379730)
高岡 宗徳 川崎医科大学, 医学部, 講師 (50548568)
羽井佐 実 川崎医科大学, 医学部, 准教授 (70322229)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 肺扁平上皮癌 / Sox2 / 人口転写因子 / 肺外科 / 分子標的治療 |
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| Outline of Final Research Achievements |
Sox2 was identified as a lineage specific oncogene, recurrently amplified in lung and esophageal squamous cell carcinoma (SCC). In this study, we have developed a zinc finger based artificial transcription factor (ATF) to suppress Sox2 expression in cancer cells and termed the system ATF/Sox2. A transient transfection reporter assay demonstrated that ATF/Sox2 repressed Sox2 transcriptional activity in Sox2 expressing lung and esophageal SCC cells. A recombinant adenoviral vector: Ad-ATF/Sox2 that expresses ATF/Sox2 suppressed Sox2 at the mRNA and protein levels in lung and esophageal SCC cells. Importantly, in these cells, Ad-ATF/Sox2 decreased cell proliferation and colony formation. Moreover, Ad-ATF/SOX2 significantly inhibited tumor growth in a lung SCC xenograft mouse model. These results indicate that Sox2 silencing by ATF/ Sox2 could lead to the development of effective molecular-targeted therapies for lung and esophageal SCC.
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Report
(4 results)
Research Products
(3 results)
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[Journal Article] SOX2 suppresses CDKN1A to sustain growth of lung squamous cell carcinoma.2016
Author(s)
Fukazawa T, Guo M, Ishida N, Yamatsuji T, Takaoka M, Yokota E, Haisa M, Miyake N, Ikeda T, Okui T, Takigawa N, Maeda Y, Naomoto Y.
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Journal Title
Scientific Reports
Volume: 6
Pages: 20113-20113
Related Report
Peer Reviewed / Open Access
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